Clinical research on emotional factors in the onset and course of infectious disease; of cancer, the resistance to which growing evidence points to as immunologic in nature; and of autoimmune diseases, which seem to be associated with states of immunologic deficiency, makes the hypothesis that stress and emotional distress may be immunosuppressive attractive. We have experimental evidence that some forms of stress can suppress antibody formation and graft-versus-host reactions, that handling in infancy can enhance adult immunologic responsivity, and that stress increases the severity of adjuvant-induced arthritis and effects the course of experimental tumors. Our basic aim is to understand the mechanisms of stress effects on immunity, both in terms of neurohumoral effectors and specific components of the immune response. We shall: 1. Investigate the effects of stress on the cellular and humoral aspects of regulation of antibody production, tolerance induction and graft-versus- host response. 2. Determine the effect of neurohumoral and psychopharmacologic agents on stress-induced changes in these systems. 3. Study the effect of hypothalamic stimulation and ablation on these systems.